When hapten-modified liposomes were "targeted" to myeloma cells or to human lymphocytes, they bound in large numbers to the cell membranes, but their contents were not internalized. However, when liposomes opsonized with IgG were presented to murine P388D1 cells, they were readily endocytosed. Uptake was specifically mediated by the Fc receptor on the cell. If methotrexate (MTX) was encapsulated in the liposomes, it escaped from the phagolysosomal apparatus to reach a cytoplasmic target and affect the physiology of the cell. We have developed a method for covalently attaching antibody and other ligands to liposomes. We have designed "temperature-sensitive" liposomes that release an entrapped drug locally at temperatures obtainable by mild hyperthermia, for example in the treatment of tumors. In the presence of serum the ratio of drug release at 43 degrees to that at 37 degrees can be made greater than 100:1. We find that (i) such liposomes deliver at least 14 times as much MTX to heated murine tumors as to unheated control tumors, (ii) the drug reaches its target enzyme in the tumor cell cytoplasm, and (iii) tumor growth can thus be delayed. With large unilamellar liposomes, serum leads to even faster and more useful release at Tc.